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Purinergic receptors as potential therapeutic targets in Alzheimer's disease

pattismith

Senior Member
Messages
3,926
@Jesse2233 , @Murph

Purinergic receptors as potential therapeutic targets in Alzheimer's disease


Fernández D1, Flores-Santibáñez F1, Neira J2,3, Osorio-Barrios F3, Tejón G1, Nuñez S1, Hidalgo Y1, Fuenzalida MJ1, Meza D1, Ureta G3, Lladser A3, Pacheco R2,3, Acuña-Castillo C4, Guixé V1, Quintana FJ5, Bono MR1, Rosemblatt M1,2,3, Sauma D1.

Abstract

T helper type 17 (Th17) lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, are present in intestinal lamina propria and have been described as important players driving intestinal inflammation.
Recent evidence, supporting the notion of a functional and phenotypic instability of Th17 cells, has shown that Th17 differentiate into type 1 regulatory (Tr1) T cells during the resolution of intestinal inflammation.
Moreover, it has been suggested that the expression of CD39 ectonucleotidase endows Th17 cells with immunosuppressive properties.
However, the exact role of CD39 ectonucleotidase in Th17 cells has not been studied in the context of intestinal inflammation.
Here we show that Th17 cells expressing CD39 ectonucleotidase can hydrolyze ATP and survive to ATP-induced cell death.

Moreover, in vitro-generated Th17 cells expressing the CD39 ectonucleotidase produce IL-10 and are less pathogenic than CD39 negative Th17 cells in a model of experimental colitis in Rag-/- mice.
Remarkably, we show that CD39 activity regulates the conversion of Th17 cells to IL-10-producing cells in vitro, which is abrogated in the presence of ATP and the CD39-specific inhibitor ARL67156.
All these data suggest that CD39 expression by Th17 cells allows the depletion of ATP and is crucial for IL-10 production and survival during the resolution of intestinal inflammation.